Date of Award

2011

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

Abstract

The long-term effects of stroke often include cognitive impairments, but other than cognitive rehabilitation, which is often not fully successful, there is no intervention to treat cognitive impairments in stroke survivors. Our laboratory has previously shown that immunotherapy directed against the Nogo-A protein, which is enriched on oligodendrocytes, improves recovery of skilled forelimb sensorimotor function in adult and aged rats after an ischemic stroke lesion to the sensorimotor cortex. Furthermore, this recovery was correlated with axonal sprouting from intact pathways to denervated areas, as well as dendritic sprouting and increased dendritic spine density in the contralateral sensorimotor cortex. In the present project we aimed to investigate whether anti-Nogo-A immunotherapy improves performance on a spatial memory task after a sensorimotor cortical stroke in aged rats. We found that rats with ischemic stroke and treated with anti-Nogo-A immunotherapy performed better on the reference memory portion of the Morris water maze than control antibody treated rats. In the hippocampus, a brain area important for spatial memory, we found a decrease in dendritic complexity on the same side as the stroke when compared to normal aged rats. However, anti-Nogo-A immunotherapy did not prevent this decrease in dendritic complexity in the hippocampus on the same side as the stroke lesion. To further investigate whether Nogo-A plays a role in dendritic structural plasticity, and specifically the Nogo-A found in neurons, we used RNA interference to reduce the levels of Nogo-A in hippocampal CA1 pyramidal cells in aged rats. We did not detect any changes in dendritic spine density and morphology. Taken together this suggests that anti-Nogo-A immunotherapy may be a successful treatment for cognitive impairments caused by stroke, although the potential neuroanatomical basis for this recovery is still under investigation.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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